Milk fat globule membrane proteins are crucial in regulating lipid digestion during simulated in vitro infant gastrointestinal digestion.

Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: One with MPL as the interfaced of lipid droplets (RE-1), one with membrane protein concentrate (MPC) (RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analyzed. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was 255.00 ± 3.54 µmol,328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more unsaturated fatty acids (USFAs) during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of USFAs, while the presence of MPC increased the release of FFA. These results show that both MPL and MP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods.

Genetic regulation of human brain proteome reveals proteins implicated in psychiatric disorders.

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate <5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

Multilayer regulatory landscape and new regulators identification for bud dormancy release and bud break in Populus.

For trees originating from boreal and temperate regions, the dormancy-to-active transition, also known as bud dormancy release and bud break, are crucial processes that allow trees to reactive growth in the spring. The molecular mechanisms underlying these two processes remain poorly understood. Here, through integrative multiomics analysis of the transcriptome, DNA methylome, and proteome, we gained insights into the reprogrammed cellular processes associated with bud dormancy release and bud break. Our findings revealed multilayer regulatory landscapes governing bud dormancy release and bud break regulation, providing a valuable reference framework for future functional studies. Based on the multiomics analysis, we have determined a novel long intergenic noncoding RNA named Phenology Responsive Intergenic lncRNA 1 (PRIR1) plays a role in the activation of bud break. that the molecular mechanism of PRIR1 has been preliminary explored, and it may partially promote bud break by activating its neighbouring gene, EXORDIUM LIKE 5 (PtEXL5), which has also been genetically confirmed as an activator for bud break. This study has revealed a lncRNA-mediated regulatory mechanism for the control of bud break in Populus, operating independently of known regulatory pathways.

Quantitative Proteomics Reveals the Relationship between Protein Changes and Volatile Flavor Formation in Hunan Bacon during Low-Temperature Smoking.

This study aimed to investigate the changes in proteins and volatile flavor compounds that occur in bacon during low-temperature smoking (LTS) and identify potential correlations between these changes. To achieve this, a combination of gas chromatography-mass spectrometry and proteomics was employed. A total of 42 volatile flavor compounds were identified in the bacon samples, and, during LTS, 11 key volatile flavor compounds with variable importance were found at a projection value of >1, including 2',4'-dihydroxyacetophenone, 4-methyl-2H-furan-5-one, Nonanal, etc. In total, 2017 proteins were quantified at different stages of LTS; correlation coefficients and KEGG analyses identified 27 down-regulated flavor-related proteins. Of these, seven were involved in the tricarboxylic acid (TCA) cycle, metabolic pathways, or amino acid metabolism, and they may be associated with the process of flavor formation. Furthermore, correlation coefficient analysis indicated that certain chemical parameters, such as the contents of free amino acids, carbonyl compounds, and TCA cycle components, were closely and positively correlated with the formation of key volatile flavor compounds. Combined with bioinformatic analysis, the results of this study provide insights into the proteins present in bacon at various stages of LTS. This study demonstrates the changes in proteins and the formation of volatile flavor compounds in bacon during LTS, along with their potential correlations, providing a theoretical basis for the development of green processing methods for Hunan bacon.

[Retracted] miR­143­5p suppresses breast cancer progression by targeting the HIF­1α­related GLUT1 pathway.

[This retracts the article DOI: 10.3892/ol.2022.13268.].

CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis.

OBJECTIVES: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear. METHODS: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1. RESULTS: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells. CONCLUSIONS: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.

MCU inhibition protects against intestinal ischemia‒reperfusion by inhibiting Drp1-dependent mitochondrial fission.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study.

OBJECTIVE: A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. METHODS: Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3 years. RESULTS: The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. CONCLUSIONS: For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

New insights into the destabilization of fat globules in ultra-instantaneous UHT milk induced by added plasmin: Molecular mechanisms and the effect of membrane structure on plasmin action.

Residual plasmin activity in whole ultra-instantaneous UHT (UI-UHT) milk causes rapid fat rise during storage, seriously affecting consumers' purchase intentions. In this work, the molecular mechanisms underlying fat destabilization in whole UI-UHT milk by added plasmin were investigated based on the hydrolysis behavior of interfacial proteins. By using SDS-PAGE and peptidomic analysis, we found that the hydrolysis of interfacial proteins by plasmin led to a decrease in the amount and coverage of interfacial proteins and an increase in zeta-potential value, causing the flocculation and coalescence of fat globules. Moreover, the hydrolysis pattern varied in different categories of interfacial proteins by plasmin. In total, 125 peptides in all samples were identified. Plasmin tended to hydrolyze most major milk fat globule membrane (MFGM) proteins into protein fragments (>10 kDa) rather than peptides (<10 kDa). In contrast, peptides derived from caseins were more preferentially identified within a relatively short incubation time. It was the co-hydrolysis of caseins and some major MFGM proteins as anchors that destroyed the stability of MFGM. Furthermore, studies on the effect of trilayer membrane structure remaining at the interface on the hydrolysis rate of major MFGM proteins by plasmin revealed that ADPH and BTN were very sensitive to plasmin action, while PAS 7 was very resistant to plasmin action. Overall, membrane structure reduced the susceptibility of some major MFGM proteins to plasmin and provided protective effects. Therefore, this study provided important insights into the hydrolysis behavior of interfacial proteins in whole UI-UHT milk induced by plasmin.

Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

The Optimization of Pair Distribution Functions for the Evaluation of the Degree of Disorder and Physical Stability in Amorphous Solids.

The amorphous form of poorly soluble drugs is physically unstable and prone to crystallization, resulting in decreased solubility and bioavailability. However, the conventional accelerated stability test for amorphous drugs is time-consuming and inaccurate. Therefore, there is an urgent need to develop rapid and accurate stability assessment technology. This study used the antitumor drug nilotinib free base as a model drug. The degree of disorder and physical stability in the amorphous form was assessed by applying the pair distribution function (PDF) and principal component analysis (PCA) methods based on powder X-ray diffraction (PXRD) data. Specifically, the assessment conditions, such as the PDF interatomic distance range, PXRD detector type, and PXRD diffraction angle range were also optimized. The results showed that more reliable PCA data could be obtained when the PDF interatomic distance range was 0-15 Å. When the PXRD detector was a semiconductor-type detector, the PDF data obtained were more accurate than other detectors. When the PXRD diffraction angle range was 5-40°, the intermolecular arrangement of the amorphous drugs could be accurately predicted. Finally, the accelerated stability test also showed that under the above-optimized conditions, this method could accurately and rapidly assess the degree of disorder and physical stability in the amorphous form of drugs, which has obvious advantages compared with the accelerated stability test.

Photoperiod-Dependent Nutrient Accumulation in Rice Cultivated in Plant Factories: A Comparative Metabolomic Analysis.

Plant factories offer a promising solution to some of the challenges facing traditional agriculture, allowing for year-round rapid production of plant-derived foods. However, the effects of conditions in plant factories on metabolic nutrients remain to be explored. In this study, we used three rice accessions (KongYu131, HuangHuaZhan, and Kam Sweet Rice) as objectives, which were planted in a plant factory with strict photoperiods that are long-day (12 h light/12 h dark) or short-day (8 h light/16 h dark). A total of 438 metabolites were detected in the harvested rice grains. The difference in photoperiod leads to a different accumulation of metabolites in rice grains. Most metabolites accumulated significantly higher levels under the short-day condition than the long-day condition. Differentially accumulated metabolites were enriched in the amino acids and vitamin B6 pathway. Asparagine, pyridoxamine, and pyridoxine are key metabolites that accumulate at higher levels in rice grains harvested from the short-day photoperiod. This study reveals the photoperiod-dependent metabolomic differences in rice cultivated in plant factories, especially the metabolic profiling of taste- and nutrition-related compounds.

Intracellular and extracellular Cyclophilin a promote cardiac fibrosis through TGF-ß signaling in response to angiotensin â ¡.

Cardiac fibrosis is characterized by abnormal proliferation of cardiac fibroblasts (CFs) and ventricular remodeling, which finally leads to heart failure. Inflammation and oxidative stress play a central role in the development of cardiac fibrosis. CyPA (Cyclophilin A) is a main proinflammatory cytokine secreted under the conditions of oxidative stress. The mechanisms by which intracellular and extracellular CyPA interact with CFs are unclear. Male C57BL/6 J mice received angiotensin Ⅱ (Ang Ⅱ) or vehicle for 4 weeks. Inhibition of CyPA significantly reversed Ang Ⅱ-induced cardiac hypertrophy and fibrosis. Mechanically, TGF-ß (Transforming growth factor-ß) signaling was found to be an indispensable downstream factor of CyPA-mediated myofibroblast differentiation and proliferation. Furthermore, intracellular CyPA and extracellular CyPA activate TGF-ß signaling through NOD-like receptor protein 3 (NLRP3) inflammasome and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, respectively. Pharmacological inhibition of CyPA and its receptor CD147 implemented by Triptolide also attenuated the expression of TGF-ß signaling and cardiac fibrosis in Ang Ⅱ-model. These studies elucidate a novel mechanism by which CyPA promotes TGF-ß and its downstream signaling in CFs and identify CyPA (both intracellular and extracellular) as plausible therapeutic targets for preventing or treating cardiac fibrosis induced by chronic Ang Ⅱ stimulation.

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3.

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Generation and applications of synthetic computed tomography images for neurosurgical planning.

OBJECTIVE: CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis. METHODS: Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a "synthetic" CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration. RESULTS: A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion. CONCLUSIONS: The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.

Numerical Simulation Study on Combustion of Low Calorific Value Waste Blended with Biomass.

Numerical simulations of a 600 t/day waste incinerator was carried out using the fluid dynamic incinerator code and Fluent to evaluate the effect of biomass blending on furnace temperature, pollutant generation, and selective noncatalytic-reduction (SNCR) denitrification when treating low calorific-value waste. The results show that as the biomass blending ratio increases, the water content gradually decreases, the calorific value increases, and the maximum temperature of the incinerator gradually increases from 1227 to 1408 K, while the content of exported NOx increases from 579 to 793 mg/Nm3; during the combustion of low-quality waste, the residence time of the flue gas in the high-temperature region (above 1123 K) is 1.62 s. When the biomass blending ratio exceeds 20%, the residence time of the flue gas in the high-temperature region is more than 2 s, which can effectively curb the generation of dioxin. When the biomass blending ratio is 20%, and the normalized stoichiometric ratio (2nurea/nNO) of urea injected into the SNCR is 1.1, the NOx concentration at the outlet is 230.08 mg/Nm3, which satisfies the NOx emission standard of less than 250 mg/Nm3.

Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Flare: An FPGA-Based Full Precision Low Power CNN Accelerator with Reconfigurable Structure.

Convolutional neural networks (CNNs) have significantly advanced various fields; however, their computational demands and power consumption have escalated, posing challenges for deployment in low-power scenarios. To address this issue and facilitate the application of CNNs in power constrained environments, the development of dedicated CNN accelerators is crucial. Prior research has predominantly concentrated on developing low precision CNN accelerators using code generated from high-level synthesis (HLS) tools. Unfortunately, these approaches often fail to efficiently utilize the computational resources of field-programmable gate arrays (FPGAs) and do not extend well to full precision scenarios. To overcome these limitations, we integrate vector dot products to unify the convolution and fully connected layers. By treating the row vector of input feature maps as the fundamental processing unit, we balance processing latency and resource consumption while eliminating data rearrangement time. Furthermore, an accurate design space exploration (DSE) model is established to identify the optimal design points for each CNN layer, and dynamic partial reconfiguration is employed to maximize each layer's access to computational resources. Our approach is validated through the implementation of AlexNet and VGG16 on 7A100T and ZU15EG platforms, respectively. We achieve an average convolutional layer throughput of 28.985 GOP/s and 246.711 GOP/s for full precision. Notably, the proposed accelerator demonstrates remarkable power efficiency, with a maximum improvement of 23.989 and 15.376 times compared to current state-of-the-art FPGA implementations.